A major Phase III clinical trial of a tau inhibitor aggregation (TAI) therapy by Singapore's TauRx failed to meet its primary endpoint, though the work showed an identified subgroup with a statistically significant benefit as a monotherapy.
The failure, reported at the Alzheimer’s Association International Conference (AAIC) in Toronto, raises questions about the prospects for a company that has bucked a focus on beta amyloid, which pharmas such as Eli Lilly ($LLY) and Pfizer ($PFE) have pursued--also unsuccessfully.
"A clinical trial of LMTM … in people with mild to moderate Alzheimer's failed to demonstrate a treatment benefit in the primary analysis of the full study population in both doses tested," the AIIC said in a press release.
"In a pre-planned analysis of a small subgroup of the study population that received LMTM as a monotherapy, there was a statistically significant benefit on cognitive and functional outcomes, and slowing of brain atrophy. The study drug is thought to reduce the accumulation of the protein tau, which normally stabilizes neurons, into potentially toxic tangles."
The company had raised over $300 million in more than a decade to pursue its efforts on TAI and was led by Claude Wischik, co-founder and executive chairman of TauRx, who identified the tau tangle pathology originally discovered by Alois Alzheimer as a point of research for a therapy.
Funding for clinical studies came from doctors in Singapore and Malaysia as well as funds from Singapore's Temasek and Malaysian casino and resort operator Genting.
A separate Phase III trial by the company on frontotemporal dementia will be released next week in Munich, according to clinical investigator Serge Gauthier, of the Departments of Neurology & Neurosurgery, Psychiatry, Medicine, at McGill University.
He is also the director of the Alzheimer Disease and Related Disorders Research Unit of the McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, and first author on the study abstract.
He did note that in cases where the subgroup showed a response, patients who had not received any other therapy may not have had access to such treatments and were geographically localized.
Gauthier added in a conference call that any future clinical work based on the trial results would depend on a detailed review of the data, while adding that the monotherapy analysis may provide a basis for designing an "appropriate and "realistic" effort.
The 15-month double-blind, placebo-controlled trial recruited 891 people from 115 sites across 16 countries in Europe, North America, Asia and Russia. The TAI therapy went up against placebo in 15% of the cohort in randomized oral doses of 150 or 250 milligrams daily.
- here's the clinicaltrials.gov link
Singapore's TauRx slated to update on PhIII Alzheimer's trials